Utilization of multimodality therapy with primary radical prostatectomy versus radiation therapy for Gleason 8–10 prostate cancer

PurposeThe role of multimodality therapy (MMT) in the treatment of Gleason 8–10 prostate cancer remains controversial. We sought to evaluate factors associated with MMT utilization for primary radical prostatectomy (RP) and primary radiation therapy (RT).Methods and MaterialsFrom the National Cancer Database, we conducted a retrospective review of 81,528 men with National Cancer Center Network Gleason 8–10 prostate cancer diagnosed between 2004 and 2015, who underwent (1) primary RP with or without early postoperative external beam RT (EBRT) or (2) primary RT (androgen deprivation therapy + EBRT) with or without brachytherapy (BT) boost. Using multivariable logistic regression models, we evaluated factors associated with the utilization of MMT, defined as early postoperative EBRT for primary RP or BT boost for primary RT.ResultsFor primary RP, the percentages of men who underwent MMT for Gleason 8 and 9–10 disease were 12.2% and 24.1%, respectively. On multivariable logistic regression, men with Gleason 9–10 were more likely to undergo MMT (odds ratio 1.03 [1.02, 1.04]), although adverse pathologic features such as T3b-4 (1.24 [1.23, 1.25]) disease demonstrated the strongest associations. For primary RT, the percentages of men who underwent BT boost for Gleason 8 and 9–10 disease were 11.8% and 9.8%, respectively. On multivariable logistic regression, men with Gleason 9–10 disease were less likely to receive BT boost (0.99 [0.98, 0.99]).ConclusionsMen with more aggressive Gleason 9 disease were more likely to undergo MMT if they underwent primary RP but not primary RT. Further blood-based or imaging biomarkers may aid in identifying optimal candidates for MMT, especially for primary RT.     

Whole-body MRI at 1.5 T and 3 T compared with FDG-PET-CT for the detection of tumour recurrence in patients with colorectal cancer

The purpose of this study was to assess the diagnostic accuracy of whole-body MRI (WB-MRI) at 1.5 T or 3 T compared with FDG-PET-CT in the follow-up of patients suffering from colorectal cancer. In a retrospective study, 24 patients with a history of colorectal cancer and suspected tumour recurrence underwent FDG-PET-CT and WB-MRI with the use of parallel imaging (PAT) for follow-up. High resolution coronal T1w-TSE and STIR sequences at four body levels, HASTE imaging of the lungs, contrast-enhanced T1w- and T2w-TSE sequences of the liver, brain, abdomen and pelvis were performed, using WB-MRI at either 1.5 T (n = 14) or 3 T (n = 10). Presence of local recurrent tumour, lymph node involvement and distant metastatic disease was confirmed using radiological follow-up within at least 5 months as a standard of reference. Seventy seven malignant foci in 17 of 24 patients (71%) were detected with both WB-MRI and PET-CT. Both investigations concordantly revealed two local recurrent tumours. PET-CT detected significantly more lymph node metastases (sensitivity 93%, n = 27/29) than WB-MRI (sensitivity 63%, n = 18/29). PET-CT and WB-MRI achieved a similar sensitivity for the detection of organ metastases with 80% and 78%, respectively (37/46 and 36/46). WB-MRI detected brain metastases in one patient. One false-positive local tumour recurrence was indicated by PET-CT. Overall diagnostic accuracy for PET-CT was 91% (sensitivity 86%, specificity 96%) and 83% for WB-MRI (sensitivity 72%, specificity 93%), respectively. Examination time for WB-MRI at 1.5 T and 3 T was 52 min and 43 min, respectively; examination time for PET-CT was 103 min. Initial results suggest that differences in accuracy for local and distant metastases detection using FDG-PET-CT and WB-MRI for integrated screening of tumour recurrence in colorectal cancer depend on the location of the malignant focus. Our results show that nodal disease is better detected using PET-CT, whereas organ disease is depicted equally well by both investigations.     

Knife or needles? A cohort analysis of outcomes after radical prostatectomy or brachytherapy for men with low- or intermediate-risk adenocarcinoma of the prostate

PurposeThe purpose of this study was to evaluate long-term outcomes for men with early stage prostate cancer treated with radical prostatectomy (RP) or brachytherapy (BT) at a single tertiary care center.Methods and MaterialsWe retrospectively analyzed data from 371 men with clinical T1a–T2c disease with prostate-specific antigen level <20 ng/mL and Gleason score (GS) 6–7 who were treated with RP (n = 279) or BT (n = 92) at MD Anderson Cancer Center in 2000–2001. Biochemical recurrence–free survival (BRFS) and prostate cancer–specific survival rates were compared by treatment modality.ResultsThe median followup time was 7.2 and 7.6 years for patients treated with RP and BT, respectively. Disease was upgraded from GS 6 to 7 after central review of the biopsy specimen for 36 men treated with RP (12.9%) and 15 men treated with BT (16.3%). After RP, GS was upgraded in 121 men (43.4%) between the centrally reviewed biopsy and the RP specimen. After RP, 5-year BRFS rates were 96.1% and 90.6% for low- and intermediate-risk disease, respectively (p = 0.003). After BT, 5-year BRFS rates were 92.5% and 95.8% for low- and intermediate-risk disease, respectively (p = 0.017). After RP or BT, 5-year BRFS rates were not significantly different with GS upgraded. Five-year prostate cancer–specific survival rates for patients with upgraded GS were 100% for both RP and BT.ConclusionsExcellent disease control outcomes can be achieved after either RP or BT as monotherapy for men with early stage prostate cancer. Upgrading of GS from 6 to 7, either (3 + 4) or (4 + 3), did not predict for worse outcomes.     

Could 68-Ga PSMA PET/CT become a new tool in the decision-making strategy of prostate cancer patients with biochemical recurrence of PSA after radical prostatectomy? A preliminary,monocentric series

Aim

To evaluate the impact of gallium68 PSMA-11 (HBED-CC)-PET/CT on decision-making strategy of patients with relapsing prostate cancer (PC) presenting a second biochemical relapse after radical prostatectomy (RP) and salvage RT or salvage androgen deprivation therapy (ADT).

Materials and methods

40 patients were retrospectively analyzed. All of them had received prostatectomy. Thirteen out of 40 were addressed to gallium68 PSMA-11 (HBED-CC)-PET/CT for a biochemical relapse after RP, 14/40 after a salvage RT and 13/40 after salvage or adjuvant ADT. The PSA level ranged between 0.1 and 1.62 ng/ml (median value: 0.51 ng/ml). We studied the impact on the decision-making process of a multidisciplinary tumor board of additional data obtained from gallium68 PSMA-11 (HBED-CC)-PET/CT.

Results

Thirty-one out of 40 evaluated patients showed positive findings at gallium68 PSMA-11 (HBED-CC)-PET/CT (77.5%). Of them, five were positive in the prostatic bed, nine in the pelvic nodes, twelve in nodes outside the pelvis and eight at bone level. Nine patients presented two different sites of relapse (22.5%). Gallium68 PSMA-11 (HBED-CC)-PET/CT data changed the therapeutic approach in 28 patients (70%).

Conclusions

Gallium68 PSMA-11 (HBED-CC)-PET/CT can be a useful tool in the restaging of post-RP, RT or ADT patients presenting biochemical relapse of PC and it could change the decision-making process in up of 70% of these patients. Prospective, larger series are needed to establish the correct role of this very promising tool in the staging and therapeutic approach of PC patients.

     

Patterns of failure after radical prostatectomy in prostate cancer – implications for radiation therapy planning after <Superscript>68</Superscript>Ga-PSMA-PET imaging

Background

Salvage radiotherapy (SRT) after radical prostatectomy (RPE) and lymphadenectomy (LAE) is the appropriate radiotherapy option for patients with persistent/ recurrent prostate cancer (PC). ⁶⁸Ga-PSMA-PET imaging has been shown to accurately detect PC lesions in a primary setting as well as for local recurrence or for lymph node (LN) metastases.

Objective

In this study we evaluated the patterns of recurrence after RPE in patients with PC, putting a highlight on the differentiation between sites that would have been covered by a standard radiation therapy (RT) field in consensus after the RTOG consensus and others that would have not.

Methods and materials

Thirty-one out of 83 patients (37%) with high-risk PC were the subject of our study. Information from ⁶⁸Ga-PSMA-PET imaging was used to individualize treatment plans to include suspicious lesions as well as possibly boost sites with tracer uptake in LN or the prostate bed. For evaluation, ⁶⁸Ga-PSMA-PET-positive LN were contoured in a patient dataset with a standard lymph drainage (RTOG consensus on CTV definition of pelvic lymph nodes) radiation field depicting color-coded nodes that would have been infield or outfield of that standard lymph drainage field and thereby visualizing typical patterns of failure of a “blind” radiation therapy after RPE and LAE.

Results

Compared to negative conventional imaging (CT/MRI), lesions suspicious for PC were detected in 27/31 cases (87.1%) by ⁶⁸Ga-PSMA-PET imaging, which resulted in changes to the radiation concept. There were 16/31 patients (51.6%) that received a simultaneous integrated boost (SIB) to a subarea of the prostate bed (in only three cases this dose escalation would have been planned without the additional knowledge of ⁶⁸Ga-PSMA-PET imaging) and 18/31 (58.1%) to uncommon (namely presacral, paravesical, pararectal, preacetabular and obturatoric) LN sites. Furthermore, 14 patients (45.2%) had a changed TNM staging result by means of ⁶⁸Ga-PSMA-PET imaging.

Conclusion

Compared to conventional CT or MRI staging, ⁶⁸Ga-PSMA-PET imaging detects more PC lesions and, thus, significantly influences radiation planning in recurrent prostate cancer patients enabling individually tailored treatment.

     

Do apparent diffusion coefficient (ADC) values obtained using high b-values with a 3-T MRI correlate better than a transrectal ultrasound (TRUS)-guided biopsy with true Gleason scores obtained from radical prostatectomy specimens for patients with prostate cancer?

Objective

To investigate the usefulness of apparent diffusion coefficient (ADC) values in predicting true Gleason scores from radical prostatectomy specimen (tGS), compared with systematic transrectal ultrasound (TRUS)-guided biopsy GS (bGS).

Materials and methods

One hundred and five patients with biopsy-proven prostate cancer underwent preoperative DWI (b-values of 0, 1000, and 2000 s/mm²) of 3-T MRI. The mean and minimum ADCs of visible tumors were calculated for either of a pair of b-values: 0 and 1000 s/mm² (ADC₁₀₀₀), or 0 and 2000 s/mm² (ADC₂₀₀₀), and relationships between the four ADC parameters and tGS evaluated for the peripheral zone (PZ) and transition zone (TZ). For multiple tumors, the dominant tumor's GS and ADCs were estimated for cancer aggressiveness assessment by computing ROC curves.

Results

Significant negative correlations were observed between tGS and mean ADC₁₀₀₀, mean ADC₂₀₀₀, minimum ADC₁₀₀₀, and minimum ADC₂₀₀₀ (r = −0.41, −0.39, −0.39, and −0.37, respectively) of 100 visible PZ tumors and 66 visible TZ tumors (r = −0.40, −0.42, −0.29, and −0.21, respectively). For distinguishing high-grade from low/intermediate-grade PZ lesions, the areas under the curve (AUCs) of mean ADC₁₀₀₀ (0.751), mean ADC₂₀₀₀ (0.710), minimum ADC₁₀₀₀ (0.768), and minimum ADC₂₀₀₀ (0.752) were similar to that of the highest bGS (0.708) (p = 0.61, p = 0.98, p = 0.47, and p = 0.60, respectively). For distinguishing high-grade from low/intermediate-grade TZ lesions, AUCs of mean ADC₁₀₀₀ (0.779), and mean ADC₂₀₀₀ (0.811) were similar to that of the highest bGS (0.805) (p = 0.83 and p = 0.97).

Conclusion

Tumor ADCs obtained with high b-values could predict prostate cancer aggressiveness as effectively as systematic TRUS-guided biopsy.     

Long-term outcomes in patients younger than 60 years of age treated with brachytherapy for prostate cancer

Purpose

The purpose of the study was to report the outcomes and late toxicities in patients younger than 60 years of age with long-term follow-up treated with low dose rate (LDR) brachytherapy for localized prostate cancer.

Methods

Between January 2000 and December 2009, 270 consecutive patients were treated with favourable localized prostate cancer; the median follow-up was 111 months (range 21–206). All patients received one implant of LDR brachytherapy. Toxicity was reported according to the Common Toxicity Criteria for Adverse Events, Version 4.0 (CTAE v4.02) by the National Cancer Institute.

Results

The overall survival according to Kaplan–Meier estimates was 99 (±1%) at 17 years. The 17-year rate for failure in tumour-free survival (TFS) was 97% (±1%), whereas for biochemical control it was 95% (±1%) at 17 years, 97% (±1%) of patients being free of local recurrence. No intraoperative or perioperative complications occurred. Acute genitourinary (GU) grade II toxicity was 4% at 12 months. No other chronic toxicity was observed after treatment. At 6 months, 94% of patients reported no change in bowel function.

Conclusions

LDR brachytherapy provides patients younger than 60 years of age with low and intermediate-risk prostate cancer excellent outcomes and has a low risk of significant long-term GU or gastrointestinal morbidity.

     

The 15-year outcomes of high-dose-rate brachytherapy for radical dose escalation in patients with prostate cancer—A benchmark for high-tech external beam radiotherapy alone?

PurposeDose escalation using high-dose-rate brachytherapy (HDR-BT) is an established treatment method for prostate cancer. First, long-term results were previously published (specific Kiel method). This study aims to evaluate 10-/15-year outcomes of Kiel Protocol 1 (1986–1992).Methods and MaterialsConformal external beam radiotherapy (EBRT) was delivered to the pelvis (50 Gy per conventional fractionation) along with an HDR boost to the prostate amounting to a combined biologic equivalent dose in 2 Gy per fraction of 117.25 Gy (α/β = 3). The HDR-BT was performed in two fractions of 15 Gy to the peripheral zone of McNeal. The EBRT-clinical target volume covered the full pelvis. The analyzed cohort totaled 122 patients. The reported end points were overall/cancer-specific survival, local recurrence/distant metastasis rates, and biochemical (BC) control rates according to American Society for Therapeutic Radiology and Oncology/Phoenix definitions. All end points were calculated using the Kaplan–Meier method and the log-rank test in univariate analyses.ResultsThe mean follow-up time was 116.8 months. The 5-, 10-, and 15-year survival rates were 81%, 62.1%, and 45% for overall survival; 92.1%, 83.1%, and 75.3% for cancer-specific survival; 92.5%, 91.4%, and 83.9% for local recurrence–free survival; and 83.8%, 81.2%, and 69.8% for distant metastasis–free survival, respectively. American Society for Therapeutic Radiology and Oncology–defined BC tumor control rates at 5, 10, and 15 years were 81.1%, 74%, and 67.8%, respectively. According to Phoenix, the BC control rates at 5, 10, and 15 years were 77.8%, 69%, and 63.6%, respectively.ConclusionsThe long-term results for the combination of HDR-BT and EBRT continue to show excellent results, providing high equivalent dose in 2 Gy per fraction and high disease control rates. These outcomes were reproducible for the extended follow-up period ranging up to 21.9 years.     

Can MR textural analysis improve the prediction of extracapsular nodal spread in patients with oral cavity cancer?

Objective

To explore the utility of MR texture analysis (MRTA) for detection of nodal extracapsular spread (ECS) in oral cavity squamous cell carcinoma (SCC).

Methods

115 patients with oral cavity SCC treated with surgery and adjuvant (chemo)radiotherapy were identified retrospectively. First-order texture parameters (entropy, skewness and kurtosis) were extracted from tumour and nodal regions of interest (ROIs) using proprietary software (TexRAD). Nodal MR features associated with ECS (flare sign, irregular capsular contour; local infiltration; nodal necrosis) were reviewed and agreed in consensus by two experienced radiologists. Diagnostic performance characteristics of MR features of ECS were compared with primary tumour and nodal MRTA prediction using histology as the gold standard. Receiver operating characteristic (ROC) and regression analyses were also performed.

Results

Nodal entropy derived from contrast-enhanced T1-weighted images was significant in predicting ECS (p?=?0.018). MR features had varying accuracy: flare sign (70%); irregular contour (71%); local infiltration (66%); and nodal necrosis (64%). Nodal entropy combined with irregular contour was the best predictor of ECS (p?=?0.004, accuracy 79%).

Conclusion

First-order nodal MRTA combined with imaging features may improve ECS prediction in oral cavity SCC.

Key Points

? Nodal MR textural analysis can aid in predicting extracapsular spread (ECS). ? Medium filter contrast-enhanced T1 nodal entropy was strongly significant in predicting ECS. ? Combining nodal entropy with irregular nodal contour improves predictive accuracy.

     

Clinical utility of apparent diffusion coefficient (ADC) values in patients with prostate cancer: Can ADC values contribute to assess the aggressiveness of prostate cancer?

Purpose

To retrospectively evaluate the relationship between apparent diffusion coefficient (ADC) values and Gleason score (GS) in prostate cancer.

Methods

A total of 60 patients who underwent radical prostatectomy for clinically localized prostate cancer were selected for this study. Diffusion‐weighted magnetic resonance (MR) images were obtained using a 1.5 T system. ADC values were analyzed between three groups: GS of 6 or less (n = 7); GS of 7 (n = 37); and GS of 8 or higher (n = 16). ADC values of the three GS groups were statistically analyzed in order to determine the relationship with GS. In the 37 patients with GS = 7 the difference in ADC values between GS 3+4 and GS 4+3 was analyzed.

Results

Median ADC values (10^?3 mm²/s) of the three GS groups were 1.04 (GS = 6 or less), 0.867 (GS = 7), and 0.729 (GS = 8 or higher). Although there was considerable overlap among the groups, the differences in ADC were statistically significant (P < 0.0001). There was a significant inverse correlation between GS and ADC values (z = ?0.437, P < 0.0005). Median ADC values (10^?3 mm²/s) of GS 3+4 and GS 4+3 patients were 0.88 and 0.814, respectively (P < 0.05).

Conclusion

ADC values showed a negative correlation with GS. Pathologically, however, there was considerable intrasubject heterogeneity. J. Magn. Reson. Imaging 2011;33:167–172. © 2010 Wiley‐Liss, Inc.

     

3 T DCE-MRI assessment of synovitis of the interphalangeal joints in patients with erosive osteoarthritis for treatment response monitoring

Objective

To study the value of 3 T dynamic contrast-enhanced (DCE)-MRI for assessment of synovitis of the interphalangeal joints in patients with erosive osteoarthritis (EOA) for treatment response monitoring.

Materials and methods

The interphalangeal joints of fingers two to five were examined at 3 T MRI in nine patients with EOA. Two musculoskeletal radiologists recorded erosions, bone marrow oedema (BME), synovitis and osteophytes. Interobserver reliability was calculated using κ statistics. In six patients, DCE-MRI time intensity curves of synovitis in two affected joints were analysed. The maximum upslope, absolute and relative enhancement of synovitis were compared with MRI after 12 months of anti-tumour necrosis factor treatment. Intraobserver reproducibility was calculated using intra-class correlation coefficient.

Results

Interobserver reliability was ‘good’ for detection of erosions (κ?=?0.70), BME (κ?=?0.77) and synovitis (κ?=?0.77), but ‘poor’ for osteophytes (κ?=?0.12). Post-treatment DCE-MRI showed decreasing maximum upslope (p?=?0.002) and absolute (p?=?0.002) and relative (p?=?0.01) enhancement compared to the initial scan. Intraobserver reproducibility of DCE-MRI was ‘almost perfect’ or ‘strong’ for all parameters.

Conclusions

3 T DCE-MRI demonstrates changes in time intensity curves of synovitis in EOA of the interphalangeal joints in a longitudinal study, indicating this technique is promising for monitoring therapy response.     

Comparison of CT,MRI and FDG-PET in response prediction of patients with locally advanced rectal cancer after multimodal preoperative therapy: Is there a benefit in using functional imaging?

The aim of this study was to compare CT, MRI and FDG-PET in the prediction of outcome of neoadjuvant radiochemotherapy in patients with locally advanced primary rectal cancer. A total of 23 patients with T3/4 rectal cancer underwent a preoperative radiochemotherapy combined with regional hyperthermia. Staging was performed using four-slice CT (n=23), 1.5-T MRI (n=10), and ¹⁸F-FDG-PET (n=23) before and 2–4 weeks after completion of neoadjuvant treatment. Response criteria were a change in T category and tumour volume for CT and MRI and a change in glucose uptake (standard uptake value) within the tumour for FDG-PET. Imaging results were compared with those of pretherapy endorectal ultrasound and histopathological findings. Histopathology showed a response to neoadjuvant therapy in 13 patients whereas 10 patients were classified as nonresponders. The mean SUV reduction in responders (60±14%) was significantly higher than in nonresponders (37±31%; P=0.030). The sensitivity and specificity of FDG-PET in identifying response was 100% (CT 54%, MRI 71%) and 60% (CT 80%, MRT 67%). Positive and negative predictive values were 77% (CT 78%, MRI 83%) and 100% (CT 57%, MRI 50%) (PET P=0.002, CT P=0.197, MRI P=0.500). These results suggest that FDG-PET is superior to CT and MRI in predicting response to preoperative multimodal treatment of locally advanced primary rectal cancer.     

Investigating the prediction value of multiparametric magnetic resonance imaging at 3 T in response to neoadjuvant chemotherapy in breast cancer

Objective

To explore the predictive value of parameters derived from diffusion-weighted imaging (DWI) and contrast-enhanced (CE)-MRI at different time-points during neoadjuvant chemotherapy (NACT) in breast cancer.

Methods

Institutional review board approval and written, informed consent from 42 breast cancer patients were obtained. The patients were investigated before and at three different time-points during neoadjuvant chemotherapy (NACT) using tumour diameter and volume from CE-MRI and ADC values obtained from drawn 2D and segmented 3D regions of interest. Prediction of pathologic complete response (pCR) was evaluated using the area under the curve (AUC) of receiver operating characteristic analysis.

Results

There was no significant difference between pathologic complete response and non-pCR in baseline size measures (p?>?0.39). Diameter change was significantly different in pCR (p?<?0.02) before the mid-therapy point. The best predictor was lesion diameter change observed before mid-therapy (AUC?=?0.93). Segmented volume was not able to differentiate between pCR and non-pCR at any time-point. The ADC values from 3D-ROI were not significantly different from 2D data (p?=?0.06). The best AUC (0.79) for pCR prediction using DWI was median ADC measured before mid-therapy of NACT.

Conclusions

The results of this study should be considered in NACT monitoring planning, especially in MRI protocol designing and time point selection.

Key Points

? Mid-therapy diameter changes are the best predictors of pCR in neoadjuvant chemotherapy. ? Volumetric measures are not strictly superior in therapy monitoring to lesion diameter. ? Size measures perform as a better predictor than ADC values.